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Cited by 315Selenium in Biological SystemsOrganoselenium and organotellurium chemistryGenomics and Rare Diseases

The DOI matches its Crossref record; 75 of the 76 references it cites were found in a registry or an index.

Mutations in the selenocysteine insertion sequence-binding protein 2 gene lead to a multisystem selenoprotein deficiency disorder in humans

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Schoenmakers, Erik, Agostini, Maura, Mitchell, Catherine, Schoenmakers, Nadia, Papp, Laura, Rajanayagam, Odelia, Padidela, Raja, Ceron-Gutierrez, Lourdes, Doffinger, Rainer, Prevosto, Claudia, Luan, Jian’an, Montano, Sergio, Lu, Jun, Castanet, Mireille, Clemons, Nick, Groeneveld, Matthijs, Castets, Perrine, Karbaschi, Mahsa, Aitken, Sri, Dixon, Adrian, Williams, Jane, Campi, Irene, Blount, Margaret, Burton, Hannah, Muntoni, Francesco, O’Donovan, Dominic, Dean, Andrew, Warren, Anne, Brierley, Charlotte, Baguley, David, Guicheney, Pascale, Fitzgerald, Rebecca, Coles, Alasdair, Gaston, Hill, Todd, Pamela, Holmgren, Arne, Khanna, Kum Kum, Cooke, Marcus, Semple, Robert, Halsall, David, Wareham, Nicholas, Schwabe, John, Grasso, Lucia, Beck-Peccoz, Paolo, Ogunko, Arthur, Dattani, Mehul, Gurnell, Mark, Chatterjee, Krishna·2010·Journal of Clinical Investigation
DOI 10.1172/jci43653PMC PMC2993594
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Abstract

Selenium, a trace element that is fundamental to human health, is incorporated into some proteins as selenocysteine (Sec), generating a family of selenoproteins. Sec incorporation is mediated by a multiprotein complex that includes Sec insertion sequence-binding protein 2 (SECISBP2; also known as SBP2). Here, we describe subjects with compound heterozygous defects in the SECISBP2 gene. These individuals have reduced synthesis of most of the 25 known human selenoproteins, resulting in a complex phenotype. Azoospermia, with failure of the latter stages of spermatogenesis, was associated with a lack of testis-enriched selenoproteins. An axial muscular dystrophy was also present, with features similar to myopathies caused by mutations in selenoprotein N (SEPN1). Cutaneous deficiencies of antioxidant selenoenzymes, increased cellular ROS, and susceptibility to ultraviolet radiation-induced oxidative damage may mediate the observed photosensitivity. Reduced levels of selenoproteins in peripheral blood cells were associated with impaired T lymphocyte proliferation, abnormal mononuclear cell cytokine secretion, and telomere shortening. Paradoxically, raised ROS in affected subjects was associated with enhanced systemic and cellular insulin sensitivity, similar to findings in mice lacking the antioxidant selenoenzyme glutathione peroxidase 1 (GPx1). Thus, mutation of SECISBP2 is associated with a multisystem disorder with defective biosynthesis of many selenoproteins, highlighting their role in diverse biological processes.

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  1. Sundaresan, 2009, J Clin Invest., 119, 2758
  2. McFadden, 2001, Noise and Health., 3, 49

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Metadata

Authors
Schoenmakers, E., Agostini, M., Mitchell, C., Schoenmakers, N., Papp, L., Rajanayagam, O., Padidela, R., Ceron-Gutierrez, L., Doffinger, R., Prevosto, C., Luan, J., Montano, S., Lu, J., Castanet, M., Clemons, N., Groeneveld, M., Castets, P., Karbaschi, M., Aitken, S., Dixon, A., Williams, J., Campi, I., Blount, M., Burton, H., Muntoni, F., O’Donovan, D., Dean, A., Warren, A., Brierley, C., Baguley, D., Guicheney, P., Fitzgerald, R., Coles, A., Gaston, H., Todd, P., Holmgren, A., Khanna, K. K., Cooke, M., Semple, R., Halsall, D., Wareham, N., Schwabe, J., Grasso, L., Beck-Peccoz, P., Ogunko, A., Dattani, M., Gurnell, M., & Chatterjee, K.
Affiliations
  • University of Cambridge (GB)
  • QIMR Berghofer Medical Research Institute (AU)
  • Great Ormond Street Hospital (GB)
  • MRC Epidemiology Unit (GB)
  • Karolinska Institutet (SE)
  • Inserm (FR)
  • University of Leicester (GB)
  • University of Pisa (IT)
  • Darent Valley Hospital (GB)
ORCID
Venue
Journal of Clinical Investigation
Publisher
American Society for Clinical Investigation
Published
2010-12-01
Volume
120
Issue
12
Pages
4220-4235
ISSN
0021-9738 (ISSN-L)
DOI
10.1172/jci43653
PMC
PMC2993594
OpenAlex
W2123186374
Cited by
315
References
76
Citations by year
2026: 8 · 2025: 10 · 2024: 18 · 2023: 11 · 2022: 24 · 2021: 17 · 2020: 23 · 2019: 23 · 2018: 23 · 2017: 18 · 2016: 24 · 2015: 22 · 2014: 21 · 2013: 27 · 2012: 19
FWCI
21.33
Type
journal article
Language
en
Open access
Locations
  • Journal of Clinical Investigation (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • QUT ePrints (Queensland University of Technology) (submittedVersion)
  • Archive ouverte UNIGE (University of Geneva) (submittedVersion, cc-by)
  • CINECA IRIS Institutial research information system (University of Pisa) (submittedVersion)
  • UCL Discovery (University College London) (submittedVersion)
  • Leicester Research Archive (University of Leicester) (submittedVersion)
  • University of Birmingham Research Portal (University of Birmingham) (submittedVersion, other-oa)
Funders
  • Wellcome Trust
  • National Institute for Health and Care Research
  • Muscular Dystrophy UK
  • Medical Research Council
  • NIHR Cambridge Biomedical Research Centre
Topics
  • Health Sciences › Nursing › Nutrition and Dietetics › Selenium in Biological Systems
  • Physical Sciences › Chemistry › Organic Chemistry › Organoselenium and organotellurium chemistry
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomics and Rare Diseases
Keywords
selenocysteine incorporation, selenoproteins, compound heterozygosity, azoospermia, spermatogenesis, muscular dystrophy, SEPN1, photosensitivity, reactive oxygen species, T cell proliferation, cytokine production, telomere shortening, insulin sensitivity, glutathione peroxidase 1, multisystem disease
MeSH terms
Adult, Aged, Amino Acid Sequence, Animals, Base Sequence, Child, Child, Preschool, DNA, Female, Hearing Loss, Sensorineural, Humans, Insulin Resistance, Male, Middle Aged, Models, Molecular, Molecular Sequence Data, Muscular Dystrophies, Mutation, Pedigree, Photosensitivity Disorders, Spermatogenesis, T-Lymphocytes, RNA-Binding Proteins, Selenocysteine, Reactive Oxygen Species, Sequence Homology, Amino Acid, Codon, Nonsense, Mutation, Missense, Selenoproteins, Mice, Azoospermia

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